Conducting biointerface of spider-net-like chitosan-adorned polyurethane/SPIONs@SrO2-fMWCNTs for bone tissue engineering and antibacterial efficacy.

In pursuit of enhancing bone cell proliferation, this study delves into the fabrication of porous scaffolds through the integration of nanomaterials. Specifically, we present the development of highly conductive chitosan (CS) nanonets on fibro-porous polyurethane (PU) bio-membranes. These nanofibers comprise functionalized multiwall carbon nanotubes (fMWCNTs), well-dispersed superparamagnetic iron oxide (SPIONs), and strontium oxide (SrO2) nanoparticles. The resulting porous scaffold exhibits remarkable interfacial biocompatibility, antibacterial properties, and load-bearing capability. Through meticulous in vitro investigations, the CS-PU/SPIONs/SrO2-fMWCNTs nanofibrous scaffolds have demonstrated a propensity to promote bone cell regeneration. Notably, the integration of these nanomaterials has been found to upregulate crucial bone-related markers, including ALP, ARS, COL-I, RUNX2, and SPP-I. The evaluation of these markers, conducted through quantitative real-time polymerase chain reaction (qRT-PCR) and immunocytochemistry, substantiates the improved cell survival and enhanced osteogenic differentiation facilitated by the integrated nanomaterials. This comprehensive analysis underscores the efficacy of CS-PU/SPIONs/SrO2-fMWCNTs bioscaffolds in promoting MC3T3-E1 cell regeneration within, thereby holding promise for advancements in bone tissue engineering and regenerative medicine.

Janus Polyurethane Adhesive Patch with Antibacterial Properties for Wound Healing.

Despite the rapid development of tissue adhesives, flaws including allergies, poor stability, and indiscriminate double-sided adhesive properties limit their application in the medical field. In this work, Janus polyurethane patches were spontaneously prepared by adjusting the difference in the functional group distribution between the top and bottom sides of the patch during emulsion drying. Consequently, poor adhesion was exhibited on the bottom surface, while the top surface can easily adhere to metals, polymers, glasses, and tissues. The difference in adhesive strength to pork skin between the two surfaces is more than 5 times. The quaternary ammonium salt and hydrophilic components on the surface of the polyurethane patch enable the rapid removal and absorption of water from the tissue surface to achieve wet adhesion. Animal experiments have demonstrated that this multifunctional Janus polyurethane patch can promote skin wound closure and healing of infected wounds. This facile and effective strategy to construct Janus polyurethane patch provides a promising method for the development of functional tissue-adhesives.

Amphiphilic nanofibrillated cellulose/polyurethane composites with antibacterial, antifouling and self-healing properties for potential catheter applications.

This study focuses on enhancing interventional medical devices, specifically catheters, using a novel composite material. Challenges like corrosion and contamination in vivo, often caused by body fluids' pH, bacteria, and proteins, lead to mechanical damage, bacterial colonization, and biofilm formation on devices like catheters. The objective of this study was to prepare a versatile composite (HFs) by designing polyurethanes (HPU) with an ionic chain extender (HIID) and blending them with amphiphilic nanofibrillated cellulose (Am-CNF). The composite leverages dynamic interactions such as hydrogen bonding and electrostatic forces, as evidenced by Molecular Mechanics (MM) calculations. The H4F0.75 composite exhibited exceptional properties: 99 % length recovery post 600 stretching cycles at 100 % strain, rapid self-healing in artificial urine, high bactericidal activity, and excellent cell viability. Moreover, mechanical aging tests and UV-vis spectral analysis confirmed the material's durability and safety. These findings suggest that the HFs composite holds significant promise for improving catheters' performance in medical applications.

Thermoplastic polyurethane/POSS nanohybrids: Synthesis, morphology, and biological properties.

Recent studies show good osteoinductive properties of polyurethanes modified with polyhedral oligomeric silsesquioxanes (POSS). In this work, three types of POSS; propanediolisobutyl-POSS (PHI-POSS), disilanolisobutyl-POSS (DSI-POSS), and octahydroxybutyl-POSS (OCTA-POSS) were chemically incorporated into linear polyurethane based on an aliphatic isocyanate, hexamethylene diisocyanate (HDI), to obtain new nanohybrid PU-POSS materials. The full conversion of POSS was confirmed by Fourier transform infrared spectroscopy (FTIR-ATR) spectra of the model reactions with pure HDI. The materials obtained were investigated by FTIR, SEM-EDS, and DSC. The DSC studies showed the thermoplasticity of the obtained materials and apparently good recovery. 30-day immersion in SBF (simulated body fluid) revealed an increase in the rate of deposition of hydroxyapatite (HAp) for the highest POSS loadings, resulting in thick layers of hydroxyapatite (~60-40 µm), and the Ca/P ratio 1.67 (even 1.785). The structure and properties of the inorganic layer depend on the type of POSS, the number of hard segments, and those containing POSS, which can be tailored by changing the HDI/poly(tetramethylene glycol) (PTMG) ratio. Furthermore, the obtained composites revealed good biocompatibility, as confirmed by cytotoxicity tests conducted on two cell lines; normal human dermal fibroblasts (NHDF) and primary human osteoblasts (HOB). Adherent cells seeded on the tested materials showed viability even after a 48-h incubation. After this time, the population of viable, and proliferating cells exceeded 90%. Bioimaging studies have shown the fibroblast and osteoblast cells were well attached to the surface of the tested materials.

In Vitro and In Vivo Assessment of the Infection Resistance and Biocompatibility of Small-Molecule-Modified Polyurethane Biomaterials.

Bacterial intracellular nucleotide second messenger signaling is involved in biofilm formation and regulates biofilm development. Interference with the bacterial nucleotide second messenger signaling provides a novel approach to control biofilm formation and limit microbial infection in medical devices. In this study, we tethered small-molecule derivatives of 4-arylazo-3,5-diamino-1H-pyrazole on polyurethane biomaterial surfaces and measured the biofilm resistance and initial biocompatibility of modified biomaterials in in vitro and in vivo settings. Results showed that small-molecule-modified surfaces significantly reduced the Staphylococcal epidermidis biofilm formation compared to unmodified surfaces and decreased the nucleotide levels of c-di-AMP in biofilm cells, suggesting that the tethered small molecules interfere with intracellular nucleotide signaling and inhibit biofilm formation. The hemocompatibility assay showed that the modified polyurethane films did not induce platelet activation or red blood cell hemolysis but significantly reduced plasma coagulation and platelet adhesion. The cytocompatibility assay with fibroblast cells showed that small-molecule-modified surfaces were noncytotoxic and cells appeared to be proliferating and growing on modified surfaces. In a 7-day subcutaneous infection rat model, the polymer samples were implanted in Wistar rats and inoculated with bacteria or PBS. Results show that modified polyurethane significantly reduced bacteria by ∼2.5 log units over unmodified films, and the modified polymers did not lead to additional irritation/toxicity to the animal tissues. Taken together, the results demonstrated that small molecules tethered on polymer surfaces remain active, and the modified polymers are biocompatible and resistant to microbial infection in vitro and in vivo.

Antimicrobial Nonisocyanate Polyurethane Foam Derived from Lignin for Wound Healing.

Medical dressings, as a cover for wounds, can replace damaged skin in the wound healing process to play a temporary barrier role, avoid or control wound infection, and provide a favorable environment for wound healing. Therefore, there is an urgent need for medical antimicrobial dressings for the treatment of chronic wounds. Although traditional polyurethane foam has been widely used in medical dressings, conventional polyurethane foams are primarily prepared using nonbiocompatible isocyanate-based compounds, which are potentially hazardous for both operators and applications in the medical field. Here, we propose nonisocyanate polyurethane foams naturally derived from lignin by enzymatic lignin alkylation, cyclic carbonation modification, and polymerization with diamine and the addition of a blowing agent. Silver nanoparticle solution was added during foaming to confer antimicrobial properties. This lignin-based nonisocyanate polyurethane/silver composite foam (named NIPU foam-silver) using a green synthesis method has good mechanical properties, which can be used to manufacture polyurethane/silver foams, and thermal and antimicrobial properties. Notably, NIPU foam-Ag showed more than 95% bactericidal efficacy against both Escherichia coli and Staphylococcus aureus within 4 h. Evaluation of in vitro wounds in mice showed that this antimicrobial composite foam rapidly promotes wound healing and repairs damaged tissue. This suggests that this biobased biodegradable antimicrobial foam has significant scope for clinical applications in wound management.

Design of 3D-Photoprintable, Bio-, and Hemocompatible Nonisocyanate Polyurethane Elastomers for Biomedical Implants.

Polyurethanes (PUs) have adjustable mechanical properties, making them suitable for a wide range of applications, including in the biomedical field. Historically, these PUs have been synthesized from isocyanates, which are toxic compounds to handle. This has encouraged the search for safer and more environmentally friendly synthetic routes, leading today to the production of nonisocyanate polyurethanes (NIPUs). Among these NIPUs, polyhydroxyurethanes (PHUs) bear additional hydroxyl groups, which are particularly attractive for derivatizing and adjusting their physicochemical properties. In this paper, polyether-based NIPU elastomers with variable stiffness are designed by functionalizing the hydroxyl groups of a poly(propylene glycol)-PHU by a cyclic carbonate carrying a pendant unsaturation, enabling them to be post-photo-cross-linked with polythiols (thiol-ene). Elastomers with remarkable mechanical properties whose stiffness can be adjusted are obtained. Thanks to the unique viscous properties of these PHU derivatives and their short gel times observed by rheology experiments, formulations for light-based three-dimensional (3D) printing have been developed. Objects were 3D-printed by digital light processing with a resolution down to the micrometer scale, demonstrating their ability to target various designs of prime importance for personalized medicine. In vitro biocompatibility tests have confirmed the noncytotoxicity of these materials for human fibroblasts. In vitro hemocompatibility tests have revealed that they do not induce hemolytic effects, they do not increase platelet adhesion, nor activate coagulation, demonstrating their potential for future applications in the cardiovascular field.

A polyurethane-based hydrophilic elastomer with multi-biological functions for small-diameter vascular grafts.

Thrombosis and intimal hyperplasia (IH) are two major problems faced by the small-diameter vascular grafts. Mimicking the native endothelium and physiological elasticity of blood vessels is considered an ideal strategy. Polyurethane (PU) is suitable for vascular grafts in mechanics because of its molecular designability and elasticity; however, it generally lacks the endothelium-like biofunctions and hydrophilicity. To solve this contradiction, a hydrophilic PU elastomer is developed by crosslinking the hydrophobic hard-segment chains containing diselenide with diaminopyrimidine-capped polyethylene glycol (PEG). In this network, the hydrophobic aggregation occurs underwater due to the uninterrupted hard-segment chains, leading to a significant self-enhancement in mechanics, which can be tailored to the elasticity similar to natural vessels by adjusting the crosslinking density. A series of in vitro studies confirm that the hydrophilicity of PEG and biological activities of aminopyrimidine and diselenide give the PU multi-biological functions similar to the native endothelium, including stable catalytic release of nitric oxide (NO) in the physiological level; anti-adhesion and anti-activation of platelets; inhibition of migration, adhesion, and proliferation of smooth muscle cells (SMCs); and antibacterial effect. In vivo studies further prove the good histocompatibility with both significant reduction in immune response and calcium deposition. STATEMENT OF SIGNIFICANCE: Constructing small-diameter vascular grafts similar to the natural vessels is considered an ideal method to solve the restenosis caused by thrombosis and intimal hyperplasia (IH). Because of the long-term stability, bulk modification is more suitable for implanted materials, however, how to achieve the biofunctions, hydrophilicity, and elasticity simultaneously is still a big challenge. In this work, a kind of polyurethane-based elastomer has been designed and prepared by crosslinking the functional long hard-segment chains with PEG soft segments. The underwater elasticity based on hydration-induced stiffening and the multi-biological functions similar to the native endothelium are compatible with natural vessels. Both in vitro and in vivo experiments demonstrate the potential of this PU as small-diameter vascular grafts.

Facile Construction of Antimicrobial Surface via One-Step Co-Deposition of Peptide Polymer and Dopamine.

The infections associated with implantable medical devices can greatly affect the therapeutic effect and impose a heavy financial burden. Therefore, it is of great significance to develop antimicrobial biomaterials for the prevention and mitigation of healthcare-associated infections. Here, a facile construction of antimicrobial surface via one-step co-deposition of peptide polymer and dopamine is reported. The co-deposition of antimicrobial peptide polymer DLL60 BLG40 with dopamine (DA) on the surface of thermoplastic polyurethane (TPU) provides peptide polymer-modified TPU surface (TPU-DLL60 BLG40 ). The antimicrobial test shows that the TPU-DLL60 BLG40 surfaces of the sheet and the catheter both exhibit potent killing of 99.9% of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). In addition, the TPU-DLL60 BLG40 surface also exhibits excellent biocompatibility. This one-step antimicrobial modification method is fast and efficient, implies promising application in surface antimicrobial modification of implantable biomaterials and medical devices.

Biodegradation of Urethane Dimethacrylate-based materials (CAD/CAM resin-ceramic composites) and its effect on the adhesion and proliferation of Streptococcus mutans.

OBJECTIVE: To investigate whether urethane dimethacrylate (UDMA) -based dental restorative materials biodegrade in the presence of Streptococcus mutans (S. mutans) and whether the monomers affect the adhesion and proliferation of S. mutans in turn. METHODS: Cholesterol esterase and pseudocholinesterase-like activities in S. mutans were detected using p-nitrophenyl substrate. Two UDMA-based CAD/CAM resin-ceramic composites, Lava Ultimate (LU) and Vita Enamic (VE), and a light-cured UDMA resin block were co-cultured with S. mutans for 14 days. Their surfaces were characterized by scanning electron microscopy and laser microscopy, and the byproducts of biodegradation were examined by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS). Then, the antimicrobial components (silver nanoparticles with quaternary ammonium salts) were added to the UDMA resin block to detect whether the biodegradation was restrained. Finally, the effect of UDMA on biofilm formation and virulence expression of S. mutans was assessed. RESULTS: Following a 14-day immersion, the LU and UDMA resin blocks' surface roughness increased. The LU and VE groups had no UDMA or its byproducts discovered, according to the UPLC-MS/MS data, whereas the light-cured UDMA block group had UDMA, urethane methacrylate (UMA), and urethane detected. The addition of antimicrobial agents showed a significant reduction in the release of UDMA. Biofilm staining experiments showed that UDMA promoted the growth of S. mutans biofilm and quantitative real-time polymerase chain reaction results indicated that 50 µg/mL UDMA significantly increase the expression of gtfB, comC, comD, comE, and gbpB genes within the biofilm. CONCLUSIONS: UDMA in the light-cured resin can be biodegraded to produce UMA and urethane under the influence of S. mutans. The formation of early biofilm can be promoted and the expression of cariogenic genes can be up-regulated by UDMA. CLINICAL SIGNIFICANCE: This study focuses for the first time on whether UDMA-based materials can undergo biodegradation and verifies from a genetic perspective that UDMA can promote the formation of S. mutans biofilms, providing a reference for the rational use of UDMA-based materials in clinical practice.

Electrospun methacrylated natural/synthetic composite membranes for gingival tissue engineering.

New functional materials for engineering gingival tissue are still in the early stages of development. Materials for such applications must maintain volume and have advantageous mechanical and biological characteristics for tissue regeneration, to be an alternative to autografts, which are the current benchmark of care. In this work, methacrylated gelatin (GelMa) was photocrosslinked with synthetic immunomodulatory methacrylated divinyl urethanes and defined monomers to generate composite scaffolds. Using a factorial design, with the synthetic monomers of a degradable polar/hydrophobic/ionic polyurethane (D-PHI) and GelMa, composite materials were electrospun with polycarbonate urethane (PCNU) and light-cured in-flight. The materials had significantly different relative hydrophilicities, with unique biodegradation profiles associated with specific formulations, thereby providing good guidance to achieving desired mechanical characteristics and scaffold resorption for gingival tissue regeneration. In accelerated esterase/collagenase degradation models, the new materials exhibited an initial rapid weight loss followed by a more gradual rate of degradation. The degradation profile allowed for the early infiltration of human adipose-derived stromal/stem cells, while still enabling the graft's structural integrity to be maintained. In conclusion, the materials provide a promising candidate platform for the regeneration of oral soft tissues, addressing the requirement of viable tissue infiltration while maintaining volume and mechanical integrity. STATEMENT OF SIGNIFICANCE: There is a need for the development of more functional and efficacious materials for the treatment of gingival recession. To address significant limitations in current material formulations, we sought to investigate the development of methacrylated gelatin (GelMa) and oligo-urethane/methacrylate monomer composite materials. A factorial design was used to electrospin four new formulations containing four to five monomers. Synthetic immunomodulatory monomers were crosslinked with GelMa and electrospun with a polycarbonate urethane resulting in unique mechanical properties, and resorption rates which align with the original design criteria for gingival tissue engineering. The materials may have applications in tissue engineering and can be readily manufactured. The findings of this work may help better direct the efforts of tissue engineering and material manufacturing.

Sustainable Janus lignin-based polyurethane biofoams with robust antibacterial activity and long-term biofilm resistance.

Conventional antibiotic therapies have been becoming less efficient due to increasingly, and sometimes fully, antibiotic-resistant bacterial strains, sometimes known as "superbacteria" or "superbugs." Thus, novel antibacterial materials to effectively inhibit or kill bacteria are crucial for humanity. As a broad-spectrum antimicrobial agent, silver nanoparticles (Ag NPs) have been the most widely commercialized of biomedical materials. However, long-term use of significant amounts of Ag NPs can be potentially harmful to human health through a condition known as argyria, in addition to being toxic to many environmental systems. It is, thus, highly necessary to reduce the amount of Ag NPs employed in medical treatments while also ensuring maintenance of antimicrobial properties, in addition to reducing the overall cost of treatment for humanitarian utilization. For this purpose, naturally sourced antimicrobial polylysine (PL) is used to partially replace Ag NPs within the materials composition. Accordingly, a series of PL, Ag NPs, and lignin-based polyurethane (LPU) composite biofoams (LPU-PL-Ag) were prepared. These proposed composite biofoams, containing at most only 2 % PL and 0.03 % Ag NPs, significantly inhibited the growth of both Gram-positive and Gram-negative bacteria within 1 h and caused irreversibly destructive bactericidal effects. Additionally, with a layer of polydimethylsiloxane (PDMS) on the surface, PDMS-LPU-PL(2 %)-Ag(0.03 %) can effectively prevent bacterial adhesion with a clearance rate of about 70 % for both bacterial biofilms within three days and a growth rate of more than 80 % for mouse fibroblasts NIH 3 T3. These lignin-based polyurethane biofoam dressings, with shorter antiseptic sterilization times and broad-spectrum antibacterial effects, are extremely advantageous for infected wound treatment and healing in clinical use.

Green preparation of antibacterial shape memory foam based on bamboo cellulose nanofibril and waterborne polyurethane for adaptive relief of plantar pressure.

This study developed an aqueous solution blending and freeze-drying method to prepare an antibacterial shape memory foam (WPPU/CNF) based on waterborne PHMG-polyurethane and cellulose nanofibers derived from bamboo in response to the increasing demand for environmentally friendly, energy conserving, and multifunctional foams. The obtained WPPU/CNF composite foam has a highly porous network structure with well-dispersed CNFs forming hydrogen bonds with the WPPU matrix, which results in a stable and rigid cell skeleton with enhanced mechanical properties (80 KPa) and anti-abrasion ability. The presence of guanidine in the polyurethane chain endowed the WPPU/CNF composite foam with an instinctive and sustained antibacterial ability against Escherichia coli and Staphylococcus aureus. The WPPU/CNF composite foam exhibited a water-sensitive shape memory function in a cyclic shape memory program because of the chemomechanical adaptability of the hydrogen-bonded network of CNFs in the elastomer matrix. The shape-fixation ratio for local compression reached 95 %, and the shape-recovery rate reached 100 %. This allows the WPPU/CNF pad prototype to reversibly adjust the undulation height to adapt to plantar ulcers, which can reduce the local plantar pressure by 60 %. This study provides an environmentally friendly strategy for cellulose-based composite fabrication and enriches the design and application of intelligent foam devices.

Osteogenic Differentiation Capacity of Dental Pulp Stem Cells on 3D Printed Polyurethane/Boric Acid Scaffold.

Additive manufacturing is growing in the area of dentistry and orthopedics due to the potential for the fabrication of individual implants. In this study, fused deposition modeling which is the most popular method was used to produce 3D scaffolds having a grid pattern from the polyurethane (PU) filament. Then, this scaffold was coated with boric acid (BA) with the thermionic vacuum arc technique. The microstructure analysis showed the macro-pores having a dimension of ~ 0.16 mm2. The BA coating increased the roughness in adverse decreased the wettability. The presence of BA on the scaffold before and after cell culture was confirmed by FESEM-EDS and ATR-FTIR. The Cell proliferation and osteogenic differentiation capacity of dental pulp stem cells (DPSCs) on uncoated and coated printed 3D PU scaffolds were also investigated. On the third day, cell viability was found to be higher (1.3-fold) in the groups containing BA. However, on the seventh day, the increase in cell proliferation in the PU+BA group was found to be less than in the other groups. According to Ca deposition analysis and Alizarin Red staining, PU+BA increased the calcium accumulation in the cells in both osteogenic induced and non-induced conditions at day 14. According to gene expression analysis, the Runx2 expression was not detected in PU+BA groups with and without differentiation medium (p ≤0.05). The expression of OCN was persistently increased up to 21-fold and 48-fold in cells on PU and PU+BA in osteogenic differentiation medium group after 14 days compared to control group (p ≤0.05). DSPP expression was observed only in PU+BA in osteogenic differentiation medium group. In line with the results that we have obtained, our 3D printed scaffolds have properties to trigger the differentiation of DPSCs cells in terms of osteogenicity.

Sustainable Routed Mxene-Based Aminolyzed PU/PCL Film for Increased Oxidative Stress and a pH-Sensitive Drug Delivery System for Anticancer Therapy.

A remarkable challenge in the anticancer drug delivery system is developing an implantable system that can improve the chemotherapeutic effect. Polyurethane is an excellent implantable substrate, with flaws in hydrophobicity. We modified polyurethane via the chemical aminolysis technique to enhance the wettability and protein interaction. The created pores can release the rutin complex incorporated in the polyurethane matrix. In this work, the hybrid polymer matrix consists of Mxene synthesized via a sustainable and simple method by introducing a toxic-free MAX phase and etchants. The incorporation of Mxene and PCL can enhance physicochemical and biological compatibility. Sustainable Mxene increases oxidative stress, cell death, and antibacterial activity, which also resulted in the Mxene@APU/PCL film. Meanwhile, the drug release with respect to pH sensitivity was demonstrated in which Mxene and Mxene@APU/PCL films showed the highest release at pH 5.2; this indicates that the prepared Mxene and aminolyzed polyurethane can function according to the biological system and release the drug from the polymer matrix on slow degradation and swellability. The Mxene and Mxene@APU/PCL films showed 93.2% drug release with oxidative stress on THP-1 cells, which causes rupturing and apoptosis of cancerous cells. The Mxene@APU/PCL film can show great potential in future implantable anticancer drug delivery systems.

Fabrication of Oleophilic Polypeptide Nanoparticle from Complexing of Cross-Linked Epsilon-poly-l-lysine with Docusate Sodium for Preparation of Bactericidal Thermoplastic Polyurethanes.

Thermoplastic polyurethanes (TPUs) are extensively utilized in the biomedical field due to their exceptional mechanical properties and biocompatibility. However, the lack of antibacterial activity limits their application ranges. Nanoscopic particle-based additives with inherent antibacterial characteristics are regarded as promising strategies to prevent biomaterials-associated infection. Herein, a novel polymeric nanoparticle is prepared, which integrates chemically cross-linked epsilon-poly-l-lysine (CPL) and anionic surfactant-docusate sodium (DS). The cross-linked epsilon-poly-l-lysine/docusate sodium (CPL/DS) nanoparticle can be well dispersed in organic solvent and a polymer matrix, which is beneficial to endowing TPUs with synergistic miscibility and antibacterial properties. An antibacterial test showed that the CPL/DS nanoparticles have strong antibacterial activity against S. aureus. Moreover, the results of antibacterial experiments in vitro revealed that almost 100% of S. aureus could be killed by CPL/DS nanoparticle-embedded TPU film with a content of 0.5 wt %. In addition, all of the CPL/DS modified TPU films showed good cytocompatibility in vitro. Consequently, this kind of CPL/DS nanoplatform has great potential to serve as a safe and high-efficient bactericidal agent for endowing biomedical devices with bactericidal property.

Biodegradable Polyurethane Scaffolds in Regeneration Therapy: Characterization and In Vivo Real-Time Degradation Monitoring by Grafted Fluorescent Tracer.

There is an urgent need to assess material degradation in situ and in real time for their promising application in regeneration therapy. However, traditional monitoring methods in vitro cannot always profile the complicated behavior in vivo. This study designed and synthesized a new biodegradable polyurethane (PU-P) scaffold with polycaprolactone glycol, isophorone diisocyanate, and l-lysine ethyl ester dihydrochloride. To monitor the degradation process of PU-P, calcein was introduced into the backbone (PU-5) as a chromophore tracing in different sites of the body and undegradable fluorescent scaffold (CPU-5) as the control group. Both PU-P and PU-5 can be enzymatically degraded, and the degradation products are molecularly small and biosafe. Meanwhile, by virtue of calcein anchoring with urethane, polymer chains of PU-5 have maintained the conformational stability and extended the system conjugation, raising a structure-induced emission effect that successfully achieved a significant enhancement in the fluorescence intensity better than pristine calcein. Evidently, unlike the weak fluorescent response of CPU-5, PU-5 and its degradation can be clearly imaged and monitored in real time after implantation in the subcutaneous tissue of nude mice. Meanwhile, the in situ osteogeneration has also been promoted after the two degradable scaffolds have been implanted in the rabbit femoral condyles and degraded with time. To sum up, the strategy of underpinning tracers into degradable polymer chains provides a possible and effective way for real-time monitoring of the degradation process of implants in vivo.

Overcoming the Dilemma of In Vivo Stable Adhesion and Sustained Degradation by the Molecular Design of Polyurethane Adhesives for Bone Fracture Repair.

Bone adhesive is a promising candidate to revolutionize the clinical treatment of bone repairs. However, several drawbacks have limited its further clinical application, such as unreliable wet adhesive performance leading to fixation failure and poor biodegradability inhibiting bone tissue growth. By incorporating catechol groups and disulfide bonds into polyurethane (PU) molecules, an injectable and porous PU adhesive is developed with both superior wet adhesion and biodegradability to facilitate the reduction and fixation of comminuted fractures and the subsequent regeneration of bone tissue. The bone adhesive can be cured within a reasonable time acceptable to a surgeon, and then the wet bone adhesive strength is near 1.30 MPa in 1 h. Finally, the wet adhesive strength to the cortical bone will achieve about 1.70 MPa, which is also five times more than nonresorbable poly(methyl methacrylate) bone cement. Besides, the cell culture experiments also indicate that the adhesives show excellent biocompatibility and osteogenic ability in vitro. Especially, it can degrade in vivo gradually and promote fracture healing in the rabbit iliac fracture model. These results demonstrate that this ingenious bone adhesive exhibits great potential in the treatment of comminuted fractures, providing fresh insights into the development of clinically applicable bone adhesives.

Design of biodegradable polyurethanes and post-modification with long alkyl chains via inhibiting biofilm formation and killing drug-resistant bacteria for the treatment of wound bacterial infection.

The development of cationic polymers that simulate antimicrobial peptides to treat bacterial infections has received much research interest. In order to obtain polymers that can not only eradicate bacteria but also inhibit biofilm formation, without inducing bacterial drug resistance, a series of cationic polymers have been developed. Despite recent progress, the chemical structures of these polymers are stable, making them recalcitrant to biodegradation and metabolism within organisms, potentially inducing long-term toxicity. To overcome this limitation, herein, a novel strategy of designing biodegradable polyurethanes with tertiary amines and quaternary ammonium salts via condensation polymerization and post-functionalizing them is reported. These polymers were found to exhibit potent antibacterial activity against Staphylococcus aureus and Escherichia coli, effectively prevent the formation of Staphylococcus aureus biofilms, act quickly and effectively against bacteria and display no resistance after repeated use. In addition, the potent in vivo antibacterial effects of these antimicrobial polyurethanes in a mouse model with methicillin-resistant Staphylococcus aureus skin infection are demonstrated.

A Temperature and pH Dual-Sensitive Multifunctional Polyurethane with Bacteria-Triggered Antibacterial Activity.

An effective and practical antibacterial strategy is to design multifunctional and stimuli-responsive materials that exhibit antibacterial activity in response to bacterial triggers. In this study, because the metabolism of Staphylococcus aureus (S. aureus) can acidify the surrounding environment and pH level can affect the lower critical solution temperature of temperature/pH dual-sensitive polymers, a monomer containing a temperature-sensitive N-isopropyl amide derivative and pH-sensitive tertiary amine groups is first synthesized. Then, the monomer is copolymerized with a polyurethane chain, and partial tertiary amine groups are quaternized to obtain bactericidal activity. The modified polyurethane exhibits temperature/pH sensitivity, antibacterial adhesion activity, bactericidal activity, and good cytocompatibility. An in situ investigation of bacterial behavior and pH changes in the bacterial suspension during the process confirms that the temperature/pH dual-sensitive polyurethane successfully achieves antibacterial activity though the metabolic activity of S. aureus without external intervention. This design concept provides a new perspective for antibacterial material design.